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First Egg Cell Successfully Reaches Full Maturity in Lab

Dr. David Albertini explains his contribution to a study documenting the first time a primitive egg cell was taken to maturity within a lab. While clinical application is still years away, this is a fertility breakthrough.

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So I’ve been asked to review some of the research that was published just last week in the Journal of Molecular Human Reproduction. It’s work that I’ve been involved with for the last nine years and it’s based on a long-term collaboration with Professor Evelyn Telfer at the University of Edinburgh Scotland.

And for those of us who actually conducted these studies, I think before getting into some of the details, what I should make clear is that the motivation to begin this line of research (actually 10-12 years ago) was to look forward at the possibility of providing young cancer patients with the opportunity to restore their fertility at a later time in life– once they’ve actually recovered from their disease. We now know that this principle, so called “fertility preservation,” is something that is being actively applied in many arenas– not simply for cancer survivors, but for women that have genetic diseases that compromise their fertility at an earlier age and that happens to be one of the major interests here at the CHR, and it’s one of the reasons that I joined the research program here several years ago.

So why all the hoopla over this work?

It takes somewhere between 90 and 100 days for an egg cell to be prepared for fertilization and being transformed into an embryo. And when you think about this on the scale of menstrual cycles, what this means is that several months before a woman will ovulate, an egg cell will begin to develop in her ovary and it will go through a very long and complicated process by which that egg cell will grow, it will acquire all of the properties that will be needed for it to become an embryo, and hopefully if it develops successfully as an embryo, when we’ve replaced that embryo back into the female reproductive tract, it will produce a pregnancy and a live birth at the end of the day.

Now scientists have for years been able to recapitulate pieces of that three-month journey, and we’ve been able to do this by taking the Correct cells out of the ovary and putting them in a plastic dish and trying to recreate the conditions that would normally develop them. But they’ve only been able to do this for brief intervals in that long 100-day development that it takes to produce an egg.

So Professor Telfair and her team initiated studies with the animal models, in fact some of our earlier studies were done using the cow ovary as a model and we developed a lot of the technology that eventually was applied to the human in this particular study and essentially what it amounted to is that pieces of ovary from women who were undergoing surgical procedures and expecting removal of their ovaries– pieces of those ovaries were frozen and upon thawing them, we were able to design a multi-step sequence of treatments that allowed for some of these very primitive eggs that would exist in the ovaries of most women to become if you will, “activated,” and once they became activated they then would grow in size, they would acquire much the machinery that the egg cell needs that makes it unique, and over a matter of 30 to 40 days, we were able if you will, to encourage the development of some of these egg cells all the way up to the state that we call “maturation.”

And it’s a very complicated end point– it requires that the cells go through all the steps of meiosis along the way. And I will tell you–and this is acknowledged in the paper– that although we were able to take an egg cell from its very earliest stage and support its development to maturity, very, very few of the eggs that we started with actually ever reached this point.

And what that bespeaks of immediately is the fact that while this was a “Proof of Principle” paper and we were certainly very proud and satisfied that after so many years of research we were able to bring just a few of these egg cells to fruition, if you will, in fact it is a technique of very low efficiency. And one of the good things about that is that it means that we understand where in the process things are going wrong so we can focus on those steps and try and improve the efficiency of the process. But in the end of the day, this truly is the very first time, in the case of the human, where a primitive egg cell has been brought to that penultimate point of maturity that could in fact and will be evaluated in future studies.

That will those eggs be able to be fertilized normally?–Number One And Number Two–Would they actually produce embryos, okay? We have a long way to go with improving the efficiency of this process. We certainly are cognizant of the fact that the genetic integrity or the genetic health of these cells would need to be established and more rigorously studied before we ever attempted to make embryos and quite honestly as I’ve suggested to others applying this clinically is some years away. It’s some years away. We anticipate some three to five years of very active research using this study as a point of departure for future work in this field.

But, for those of us here at the CHR, the significance of this work really plays out in both the clinical realm, but also in terms of the research activities of the CHR. From the clinical perspective, the CHR has a worldwide reputation for having come to grips with some of the causes of Premature Ovarian Failure. That is, you know, why is it that some women precociously approach menopause and lose their ability to reproduce at a relatively young age?

And also, I think a major clinical emphasis at the CHR has over the years been How do we manage the aging ovary? Because with advancing maternal age, we’ve come to understand that both the number and the quality of the eggs that can be collected from from the ovaries seem to suffer from very serious consequences having to do with internal changes in the ovary itself and changes in the hormonal status of women as they age. Well, this kind of study really gives us insights into the basic process of how an egg develops and one of the things that we’ve already seen at the CHR is that the eggs that are retrieved from older women seem to have missed out on part of this three-month education period that normally goes on in the ovary. It seems as if things have been speeded up and so by the time the eggs are ready to be retrieved and fertilized, they haven’t quite finished a college education is one way you could look at it. And so you know much of our current clinical work is aimed at trying to establish conditions that would improve the quality of these eggs. And there are some take-home messages from this research that we are already exploring here at the CHR and you know we hope we’ll be helpful in improving the pregnancy rates for our for our patients.

On the research front, this work really establishes a solid foundation for moving the work forward that’s being done here on the genetic causes of ovarian aging, the genetic causes of premature ovarian failure, and with any luck and and the kinds of collaborations that we’re establishing in the area, we’ll be able to use some of the technology that’s been developed in this paper for our own studies, and that’s you know one of my specific goals in my capacity here at the CHR is to translate that technology that’s been used to really make this accomplishment to now make it more available not only to our research activities here at the CHR, but in other institutions where there’s a great deal of interest right now in not only trying to repeat our studies– which is a very, very important determinant in in the science world, we want other people to be able to reproduce our results– but also to move this technology forward so that someday we may indeed have it in a position so that it will be used by patients to increase their fertility chances.